miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis.

TitlemiR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis.
Publication TypeJournal Article
Year of Publication2018
AuthorsWang, L, E Wang, Y Wang, R Mines, K Xiang, Z Sun, G Zhou, K-Y Chen, N Rakhilin, S Chao, G Ye, Z Wu, H Yan, H Shen, J Everitt, P Bu, and X Shen
JournalElife
Volume7
Date Published12/2018
Abstract

Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to protect the inflammatory stem cell niche and reparative regeneration. Although playing little role in regular homeostasis, miR-34a deficiency leads to colon tumorigenesis after Citrobacter rodentium infection. miR-34a targets both immune and epithelial cells to restrain inflammation-induced stem cell proliferation. miR-34a targets Interleukin six receptor (IL-6R) and Interleukin 23 receptor (IL-23R) to suppress T helper 17 (Th17) cell differentiation and expansion, targets chemokine CCL22 to hinder Th17 cell recruitment to the colon epithelium, and targets an orphan receptor Interleukin 17 receptor D (IL-17RD) to inhibit IL-17-induced stem cell proliferation. Our study highlights the importance of microRNAs in protecting the stem cell niche during inflammation despite their lack of function in regular tissue homeostasis.

DOI10.7554/eLife.39479
Short TitleElife